Novel non-stop variant of the NR0B1 gene in two siblings with adrenal hypoplasia congenita
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Tomoko Ota
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Noriyuki Katsumata
Abstract
Objectives
Mutations in the dosage-sensitive sex reversal-AHC critical region on the X chromosome, gene 1 (DAX-1, officially NR0B1), cause X-linked adrenal hypoplasia congenita (AHC) and hypogonadotropic hypogonadism (HHG). Salt-losing adrenal insufficiency usually occurs during the neonatal period or early childhood. We report a novel non-stop variant of NR0B1 in two siblings and their unusual clinical course.
Case presentation
The proband was a boy who presented with an unusual form of AHC with neonatal onset of growth failure and mild salt loss, but without cutaneous pigmentation or plasma ACTH elevation. His 4-year-old elder brother had been growing healthily, but carried an AHC diagnosis. A non-stop variant of NR0B1 (p.*471K) was demonstrated in the patients and their mother.
Conclusions
We identified a novel non-stop variant of NR0B1 in two siblings. Mild salt loss associated with hyperkalemia is a crucial diagnostic clue for AHC, even without apparent symptoms of glucocorticoid deficiency.
Funding source: JSPS KAKENHI
Award Identifier / Grant number: 16K10005 (to YN and NK) and JP17K10091 (to NK)
Funding source: a Health and Labor Sciences Research Grant for research on intractable diseases from the Ministry of Health, Labor and Welfare of Japan
Award Identifier / Grant number: Nanbyo-Ippan-046 to NK
Acknowledgments
The authors thank the patient’s family for genetic testing. The authors also thank Ms. Atsuko Nagashima–Miyokawa for her excellent technical assistance.
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Research funding: This work was supported by JSPS KAKENHI Grant Numbers 16K10005 (to YN and NK) and JP17K10091 (to NK) and a Health and Labor Sciences Research Grant for research on intractable diseases from the Ministry of Health, Labor and Welfare of Japan (Nanbyo-Ippan-046 to NK).
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Author contribution: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.
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Competing interests: The authors declare no conflicts of interest.
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Informed consent: Written informed consent for the genetic analysis and publication was obtained from the parents.
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Ethical approval: The genetic study was approved by the Institutional Ethics Review Board at the National Center for Child Health and Development.
References
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Supplementary Material
The online version of this article offers supplementary material (https://doi.org/10.1515/jpem-2022-0120).
© 2022 Walter de Gruyter GmbH, Berlin/Boston
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Artikel in diesem Heft
- Frontmatter
- Review Article
- Effects and dose-response relationships of exercise intervention on weight loss in overweight and obese children: a meta-regression and system review
- Original Articles
- Diabetic ketoacidosis in children with new-onset type 1 diabetes mellitus: demographics, risk factors and outcome: an 11 year review in Hong Kong
- Incidence tendency, etiological classification and outcome of congenital hypothyroidism in Guangzhou, China: an 11-year retrospective population-based study
- Metabolically healthy obesity in a paediatric obesity clinic
- Universal salt iodization potentially contributes to health equity: socio-economic status of children does not affect iodine status
- Association between clinical variations and copy number variations in cases with Turner syndrome
- The mediating function of obesity on endocrine-disrupting chemicals and insulin resistance in children
- Relationship between prolactin level and puberty in girls with early breast development
- Pattern of presentation of paediatric endocrine disorders in a Nigerian tertiary institution: an 11-year survey
- Case Reports
- Novel non-stop variant of the NR0B1 gene in two siblings with adrenal hypoplasia congenita
- Identification of two novel ACAT1 variant associated with beta-ketothiolase deficiency in a 9-month-old boy
- Craniosynostosis in a patient with Fanconi–Bickel syndrome: a case report
- Severe loss of adipose tissue in a Vietnamese lipodystrophy patient caused by LMNA p.G465D mutation: a first clinical characterization and two-year follow-up
- The response to growth hormone treatment in a child with short stature, growth hormone deficiency and autosomal dominant cutis laxa type 3 – case report
- Novel homozygous inactivating mutation in the luteinizing hormone receptor gene (LHCGR) associated with 46, XY DSD in a Moroccan family
